English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Effective Eradication of Gliioblastoma Stem Cells by Local Application of AC133/CD133-Specific T-cell Engaging Antibody and CD8 T Cells

MPS-Authors
/persons/resource/persons191219

Mittler,  G.
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Prasad, S., Gaedicke, S., Machein, M., Mittler, G., Braun, F., Hettich, M., et al. (2015). Effective Eradication of Gliioblastoma Stem Cells by Local Application of AC133/CD133-Specific T-cell Engaging Antibody and CD8 T Cells. Cancer research: an official organ of the American Association for Cancer Research, 75, 2166-2176. doi:doi: 10.1158/0008-5472.


Cite as: http://hdl.handle.net/someHandle/test/escidoc:902581
Abstract
Cancer stem cells (CSC) drive tumorigenesis and contribute to genotoxic therapy resistance, diffuse infiltrative invasion, and immunosuppression, which are key factors for the incurability of glioblastoma multiforme (GBM). The AC133 epitope of CD133 is an important CSC marker for GBM and other tumor entities. Here, we report the development and preclinical evaluation of a recombinant AC133×CD3 bispecific antibody (bsAb) that redirects human polyclonal T cells to AC133+ GBM stem cells (GBM-SC), inducing their strong targeted lysis. This novel bsAb prevented the outgrowth of AC133-positive subcutaneous GBM xenografts. Moreover, upon intracerebral infusion along with the local application of human CD8+ T cells, it exhibited potent activity in prophylactic and treatment models of orthotopic GBM-SC-derived invasive brain tumors. In contrast, normal hematopoietic stem cells, some of which are AC133-positive, were virtually unaffected at bsAb concentrations effective against GBM-SCs and retained their colony-forming abilities. In conclusion, our data demonstrate the high activity of this new bsAb against patient-derived AC133-positive GBM-SCs in models of local therapy of highly invasive GBM.